Epigenetic frontiers: miRNAs, long non-coding RNAs and nanomaterials are pioneering to cancer therapy.

Cancer has arisen from both genetic mutations and epigenetic changes, making epigenetics a crucial area of research for innovative cancer prevention and treatment strategies. This dual perspective has propelled epigenetics into the forefront of cancer research. This review highlights the important roles of DNA methylation, histone modifications and non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long non-coding RNAs, which are key regulators of cancer-related gene expression. It explores the potential of epigenetic-based therapies to revolutionize patient outcomes by selectively modulating specific epigenetic markers involved in tumorigenesis. The review examines promising epigenetic biomarkers for early cancer detection and prognosis. It also highlights recent progress in oligonucleotide-based therapies, including antisense oligonucleotides (ASOs) and antimiRs, to precisely modulate epigenetic processes. Furthermore, the concept of epigenetic editing is discussed, providing insight into the future role of precision medicine for cancer patients. The integration of nanomedicine into cancer therapy has been explored and offers innovative approaches to improve therapeutic efficacy. This comprehensive review of recent advances in epigenetic-based cancer therapy seeks to advance the field of precision oncology, ultimately culminating in improved patient outcomes in the fight against cancer.

Investigating protein C and S levels in pregnant women with recurrent early pregnancy loss versus normal pregnancy.

Miscarriage in the first and second trimesters of pregnancy is very common, and coagulopathy can be a contributing factor. Protein C and S deficiency are rare, inherited disorders that can increase the risk of thrombophilia. Women with these deficiencies have a higher risk of developing blood clots in the placenta, which can lead to placental insufficiency and, ultimately, to a miscarriage. We aimed to compare the levels of protein C and protein S in pregnant females with recurrent first and second-trimester pregnancy loss and normal pregnant females. We performed a detailed history, examination, and various lab tests on a cohort of 40 females with a history of recurrent first and second-trimester abortions visiting an outpatient clinic at a multi-specialty hospital in Kashmir, India. All the findings were compared with 40 women with normal pregnancies. 10% of the participants had low protein C and S levels (P=0.277), out of whom 75% (p<0.001) had intrauterine growth retardation (IUGR) on ultrasound with 67% (p<0.001) having reduced doppler flow in the umbilical artery. 0.05% of participants had isolated protein S deficiency with no concomitant IUGR seen. Patients with protein C and S deficiencies were treated with heparin and progesterone and followed up for pregnancy outcomes. Screening for protein C and S deficiency is mandatory in all cases of recurrent pregnancy loss. Treatment with low molecular weight heparin and progesterone should be initiated to ensure good fetal outcomes and prevent post-partum/postoperative catastrophic venous thromboembolism events.

Hipotiroidismo subclínico y pérdida de embarazo: una revisión de la literatura / Subclinical Hypothyroidism and Pregnancy Loss: A Literature Review

Existe una alta prevalencia de hipotiroidismo subclínico (SCH) en el embarazo. Está vinculado a una importante morbilidad y mortalidad materna y fetal. Los efectos de SCH sobre el embarazo incluyen mayores riesgos de hipertensión gestacional y ruptura prematura de membranas (PROM). Sus fetos y bebés tenían más probabilidades de sufrir de bajo peso al nacer (LBW) y retraso del crecimiento intrauterino (IUGR). El riesgo de aborto espontáneo se informa alto en varios estudios para SCH no tratado. SCH se asocia directamente con una mayor presencia de anti -cuerpos anti TPO en suero materno. La detección temprana y el tratamiento de SCH han sido testigos de mejores resultados en términos de resultado del embarazo. Esta revisión se centra para establecer la relación de una mayor prevalencia de SCH en los países en desarrollo, así como su asociación con el aumento de los cuerpos anti TPO en suero materna y sacar una conclusión que puede ayudar a reducir las razones y proporcionar una solución. Este estudio concluyó que SCH es más frecuente en los países en desarrollo, ya sea debido a la deficiencia de yodo, una disminución de la conciencia sobre este problema o menos acceso a las instalaciones médicas. Por lo tanto, se sugiere que las hembras con antecedentes de partos prematuros, IUGR anteriores o abortos involuntarios deben someterse a una detección de hipotiroidismo subclínico y niveles de anticuerpos anti TPO durante sus visitas prenatales

There is a high prevalence of subclinical hypothyroidism (SCH) in pregnancy. It is linked to significant maternal and fetal morbidity and mortality. SCH's effects on pregnancy include increased risks of gestational hypertension and premature rupture of membranes (PROM). Their fetuses and infants had been more likely to suffer from low birth weight (LBW) and intrauterine growth retardation (IUGR). The risk of miscarriage is reported high in various studies for untreated SCH. SCH is directly associated with increased presence of anti TPO anti bodies in maternal serum. Early detection and treatment of SCH have witnessed better results in terms of pregnancy outcome. This review focuses to establish the relationship of increased prevalence of SCH in the developing countries as well as its association with increased anti TPO anti bodies in maternal serum and draw a conclusion which can help narrow down the reasons and provide solution. This study concluded that SCH is more prevalent in developing countries, either due to iodine deficiency, decreased awareness about this problem or less access to medical facilities. Therefore, it is suggested that females with history of preterm deliveries, previous IUGRs, or miscarriages should undergo screening for subclinical hypothyroidism and Anti TPO antibody levels during their antenatal visits.

UNA ENCUESTA DE CONOCIMIENTOS, ACTITUDES Y MEDIDAS PREVENTIVAS TOMADAS POR ESTUDIANTES DE MEDICINA Y ODONTOLOGÍA DURANTE LA PANDEMIA DE COVID-19 EN RIAD, ARABIA SAUDÍ / A Survey of Knowledge, Attitude, and Preventive Measures Taken by Medical and Dental Students during the COVID-19 Pandemic in Riyadh, Saudi Arabia

Objetivo: Con la enfermedad del coronavirus-2019 (COVID-19) convirtiéndose en una aflicción global, es imperativo evaluar el conocimiento, la actitud y las prácticas de los incipientes profesionales de la salud ante la pandemia. Por lo tanto, este estudio tuvo como objetivo evaluar el conocimiento y la actitud de los estudiantes de medicina y odontología frente a la infección COVID-19. Además, se analizaron las medidas preventivas ejercidas por ellos durante el brote. Método: Este estudio fue un estudio prospectivo, transversal, basado en un cuestionario. Se llevó a cabo en un período de 5 meses desde el 15 de abril de 2021 hasta el 15 de septiembre de 2021. Se difundió un cuestionario autoadministrado bien diseñado y validado a través de la plataforma Google Forms a 726 estudiantes de medicina y odontología de Riyadh, Arabia Saudita, después de obtener el consentimiento informado electrónico. Resultado: De los 726 encuestados, 490 eran mujeres y 236 hombres. Según los resultados, >50% de la población del estudio siguió al Ministerio de Salud, KSA, como su fuente de información para obtener las últimas actualizaciones sobre la infección por COVID-19, el 17,8% confió en las actualizaciones de la Organización Mundial de la Salud y el 17,1% recurrió a la red social actualizaciones Se encontró que el 92,33% de los estudiantes de medicina y odontología tenían un conocimiento adecuado de la pandemia y que el 96,55% demostró una actitud positiva hacia esto. Además, el 81,84% de los participantes adoptaron buenas prácticas con respecto a la infección. Conclusión: El presente estudio estableció que los estudiantes de medicina y odontología de Riyadh, Arabia Saudita, tienen un conocimiento adecuado sobre la pandemia. Los estudiantes también mostraron una actitud positiva hacia la situación. Sin embargo, con la disminución de la tasa de infección, las medidas prácticas se han reducido.

Objective: With coronavirus disease-2019 (COVID-19) becoming a global affliction, it is imperative to assess the knowledge, attitude, and practices of budding healthcare professionals toward the pandemic. Hence, this study aimed to evaluate the knowledge and attitude of medical and dental students toward COVID-19 infection. In addition, the preventive measures exercised by them during the outbreak were analyzed. Method: This study was a prospective, cross-sectional, questionnaire-based study. It was conducted over a period of 5 months from April 15, 2021 to September 15, 2021. A well-designed and validated self-administered questionnaire was disseminated through the Google Forms platform to 726 medical and dental students of Riyadh, Saudi Arabia, after obtaining electronic informed consent. Result: Of the 726 respondents, 490 were women and 236 were men. As per the results, >50% of the study population followed the Ministry of Health, KSA, as their source of information to obtain latest updates on COVID-19 infection, 17.8% relied on the World Health Organization updates, and 17.1% resorted to social network updates. It was found that 92.33% of the medical and dental students had adequate knowledge of the pandemic and that 96.55% demonstrated a positive attitude toward it. Furthermore, 81.84% of the participants adopted good practices with regard to the infection. Conclusion: The present study established that the medical and dental students of Riyadh, Saudi Arabia, have an adequate knowledge about the pandemic. The students also displayed a positive attitude toward the situation. However, with the decline in the infection rate, the practice measures have been reduced.

Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins interact with the eukaryotic translation machinery, and inhibitors of translation have potent antiviral effects. We found that the drug plitidepsin (aplidin), which has limited clinical approval, possesses antiviral activity (90% inhibitory concentration = 0.88 nM) that is more potent than remdesivir against SARS-CoV-2 in vitro by a factor of 27.5, with limited toxicity in cell culture. Through the use of a drug-resistant mutant, we show that the antiviral activity of plitidepsin against SARS-CoV-2 is mediated through inhibition of the known target eEF1A (eukaryotic translation elongation factor 1A). We demonstrate the in vivo efficacy of plitidepsin treatment in two mouse models of SARS-CoV-2 infection with a reduction of viral replication in the lungs by two orders of magnitude using prophylactic treatment. Our results indicate that plitidepsin is a promising therapeutic candidate for COVID-19.

The Global Phosphorylation Landscape of SARS-CoV-2 Infection.

The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.

The Landscape of Human Cancer Proteins Targeted by SARS-CoV-2.

The mapping of SARS-CoV-2 human protein-protein interactions by Gordon and colleagues revealed druggable targets that are hijacked by the virus. Here, we highlight several oncogenic pathways identified at the host-virus interface of SARS-CoV-2 to enable cancer biologists to apply their knowledge for rapid drug repurposing to treat COVID-19, and help inform the response to potential long-term complications of the disease.

Role of Iron and Copper in the Pathogenesis of Parkinson's Disease.

Parkinson's disease (PD) is an old age disorder of basal ganglia which involves oligomerization of α-synuclein protein and formation of intercellular inclusions known as "Lewy bodies" in substantia nigra and caudate nuclei in brain which is progressive in nature. It is second most prevalent neurodegenerative disorder characterized by tremor at rest, muscle rigidity, slowness of movement (bradykinesia, akinesia), and changes in posture (instability). Both excess and deficiency in levels of transition metals (especially iron, copper) can be detrimental to the central nervous system. Abnormalities in iron (Fe) and copper (Cu) metabolism have been reported to produce oxidative stress which is one of the major cause in pathogenesis of PD. In the present study 35 PD patients and 33 controls of Northern Indian population were included and serum levels of Fe, Cu and ceruloplasmin (Cp) were measured. Serum Fe (p < 0.01) and Cu (p < 0.01) levels were found to be significantly decreased in PD, whereas there was no significant change in Cp levels in PD patients as compared to controls. These results suggest the existence of a defect in iron which over the time, may hasten the entry of iron into the brain and decrease iron in the extracellular compartment in PD patients.

Ocular Surface Squamous Neoplasia in 200 Patients: A Case-Control Study of Immunosuppression Resulting from Human Immunodeficiency Virus versus Immunocompetency.

PURPOSE: To describe and compare the clinical presentation, treatment outcomes, and histopathologic features of ocular surface squamous neoplasia (OSSN) based on human immunodeficiency virus (HIV) status. DESIGN: Case-control study. PARTICIPANTS: A total of 200 patients with OSSN, of whom 83 (41%) had positive results for HIV and were classified as cases and 117 (59%) had negative results for HIV and were classified as controls. METHODS: Enzyme-linked immunosorbent assay for HIV, conjuntival excision biopsy, extended enucleation, orbital exenteration. MAIN OUTCOME MEASURES: Clinical features, treatment outcomes, and histopathologic characteristics. RESULTS: The mean age at presentation of OSSN in both cases and controls was 40 years (median, 40 years; range, 13-65 years) and in controls was 40 years (median, 38 years; range, 15-80 years). On comparison of cases versus controls with OSSN, HIV-positive individuals had larger (12 vs. 8 mm; P < 0.001) and thicker (3.2 vs. 2.3 mm; P = 0.041) tumors, with a higher incidence of corneal (60% vs. 40%; P = 0.007), scleral (19% vs. 9%; P = 0.044), and orbital (13% vs. 3%; P = 0.019) invasion and a higher need for extended enucleation or exenteration (27% vs. 11%; P < 0.001). The bilateral presentation (11% vs. 4%; P = 0.13), need for lamellar sclerectomy (13% vs. 8%; P = 0.29), and tumor recurrence after primary treatment (30% vs. 20%; P = 0.12) was higher in HIV-positive cases compared with HIV-negative controls. However, these features were not statistically significant. Based on American Joint Committee on Cancer classification, T1 tumor was more common in controls (13% in cases vs. 35% in controls; P = 0.0009), and T4 tumor was more common in cases (13% in cases vs. 4% in controls; P = 0.019). None of the patients demonstrated systemic metastases or died of disease during a mean follow-up period of 10 months (median, 4 months; range, <1-75 months) in cases and 9 months (median, 4 months; range, <1-99 months) in controls. CONCLUSIONS: Ocular surface squamous neoplasia in HIV-positive individuals is aggressive with larger and thicker tumors and with higher incidence of corneal, scleral, and orbital invasion. These patients are associated with poor ocular prognosis with higher need for extended enucleation, exenteration, or both.

Lateral eyelid rotation flap: a novel technique for reconstruction of full thickness eyelid defect.

The purpose of this study was to study anatomical, functional, and cosmetic outcomes of a novel technique, 'Lateral Eyelid Rotation Flap' for reconstruction of full thickness eyelid defect. In this prospective interventional study, 10 patients with full thickness eyelid defect measuring 1/2-2/3rd of eyelid width were included. Eyelid reconstruction was performed by single surgeon, using lateral eyelid rotation flap. Anatomic outcome was assessed by analyzing horizontal and vertical palpebral apertures (HPA and VPA), eyelid contour, and lateral canthus. Functional outcome was assessed by measuring tear film break-up time (TBUT) and Schirmer's test in both the eyes. Cosmetic outcome was evaluated by patients. Median age of patients was 56 years. Nine cases had full thickness defect following the excision of eyelid malignancy. The mean horizontal defect size was 17 ± 4.2 mm. HPA did not change significantly after surgery. VPA was statistically comparable to contralateral eye at 1-month follow-up. Lateral canthus angle recovered by 3rd month after surgery. TBUT and Schirmer's tests were comparable to contralateral eye. Eight patients graded cosmetic outcome as good to excellent. This is a new, single-stage technique for reconstruction of full thickness eyelid defects, with full thickness eyelid tissue including margin.

Foam sclerotherapy for periorbital dermoid cysts.

PURPOSE: To report nonsurgical treatment of periorbital dermoid cysts with foam sclerotherapy using sodium tetradecyl sulfate (STS). METHODS: Single-center, retrospective, interventional case series. Clinical records of all patients diagnosed to have congenital orbital dermoid cyst and treated with STS foam sclerotherapy between 2012 and 2013 were reviewed. The ectodermal contents of the dermoid cyst were aspirated through a stab incision with 18G needle, followed by saline lavage. Intraluminal foam sclerotherapy was then performed using STS (30 mg/ml) in a proportion of 10% of the total aspirate volume. Retrospective data analysis included demographic profile, clinicoradiologic findings, and treatment outcomes of foam sclerotherapy. RESULTS: Four patients were treated in the given period. Average age at presentation was 20.2 years. All cysts were reported to be congenital in nature, and the location was medial angular in 2 cases, lateral angular in 1 case, and lateral orbitotemporal in 1 case. The average aspirate of the pultaceous cyst content was 3.75 ml (range, 2-5 ml). Of the 4 patients, 2 dermoid cysts resolved completely within 8 weeks. Two cysts showed partial response and required a second foam sclerotherapy to achieve complete resolution. At an average follow up of 13.25 months (range, 11-16 months), complete cyst resolution was noted. No sclerotherapy-related complications were observed. CONCLUSIONS: Foam sclerotherapy is successful in obliterating periorbital dermoid cysts and provides a minimally invasive nonsurgical approach to achieve an aesthetic result.

Lacrimal gland amyloidosis: a clinicopathological correlation of a rare disorder and review of literature.

PURPOSE: To report a rare case of primary localized lacrimal gland amyloidosis and present a detailed review of the literature. METHOD: A 72-year-old woman presented with painless mass of 3 years' duration in the supero-temporal left orbit arising from the lacrimal gland. The patient underwent an excision biopsy and a further systemic workup and was diagnosed to have a primary, localized lacrimal gland amyloidosis. Only 18 cases have been reported in the literature. Based on the published cases and the present case, the clinical profiles, radiological features, and outcomes of this infrequent entity are discussed. CONCLUSION: Lacrimal gland amyloidosis, although rare, should be a differential diagnosis for a lacrimal gland mass, especially in elderly females. Review of the literature provides a clearer understanding of the presentations and management.

Disulphide bridges of phospholipase C of Chlamydomonas reinhardtii modulates lipid interaction and dimer stability.

BACKGROUND: Phospholipase C (PLC) is an enzyme that plays pivotal role in a number of signaling cascades. These are active in the plasma membrane and triggers cellular responses by catalyzing the hydrolysis of membrane phospholipids and thereby generating the secondary messengers. Phosphatidylinositol-PLC (PI-PLC) specifically interacts with phosphoinositide and/or phosphoinositol and catalyzes specific cleavage of sn-3- phosphodiester bond. Several isoforms of PLC are known to form and function as dimer but very little is known about the molecular basis of the dimerization and its importance in the lipid interaction. PRINCIPAL FINDINGS: We herein report that, the disruption of disulphide bond of a novel PI-specific PLC of C. reinhardtii (CrPLC) can modulate its interaction affinity with a set of phospholipids and also the stability of its dimer. CrPLC was found to form a mixture of higher oligomeric states with monomer and dimer as major species. Dimer adduct of CrPLC disappeared in the presence of DTT, which suggested the involvement of disulphide bond(s) in CrPLC oligomerization. Dimer-monomer equilibrium studies with the isolated fractions of CrPLC monomer and dimer supported the involvement of covalent forces in the dimerization of CrPLC. A disulphide bridge was found to be responsible for the dimerization and Cys7 seems to be involved in the formation of the disulphide bond. This crucial disulphide bond also modulated the lipid affinity of CrPLC. Oligomers of CrPLC were also captured in in vivo condition. CrPLC was mainly found to be localized in the plasma membrane of the cell. The cell surface localization of CrPLC may have significant implication in the downstream regulatory function of CrPLC. SIGNIFICANCE: This study helps in establishing the role of CrPLC (or similar proteins) in the quaternary structure of the molecule its affinities during lipid interactions.

Expression of terpenoid indole alkaloid biosynthetic pathway genes corresponds to accumulation of related alkaloids in Catharanthus roseus (L.) G. Don.

Madagascar periwinkle, Catharanthus roseus (L.) G. Don, a medicinally important plant, produces anticancer dimeric alkaloids, vinblastine and vincristine, in the leaves and accumulates antihypertensive alkaloids, ajmalicine and serpentine, in the roots. This plant grows wild in distant tropical and sub-tropical geographical locations with different agro-climates and shows wide variations in morphological and alkaloid yield-related traits. In order to understand the correlation between the expression of terpenoid indole alkaloid (TIA) pathway genes and accumulation of related alkaloids, six different genetic resources of C. roseus, including the medicinal cultivars Nirmal, Prabal, Dhawal, the mutants gsr-3 and gsr-6, and one horticultural variety, Pacifica blush, were studied. The expression profiles of one early and two late TIA biosynthetic pathway genes, namely, strictosidine synthase, desacetoxyvindoline 4-hydroxylase and deacetyl vindoline 4-O-acetyl transferase were analyzed in these plants. A positive correlation between transcript abundance and accumulation of related alkaloids was observed in the different genetic resources. The potential of these TIA biosynthetic pathway genes for use in screening of high-yielding C. roseus germplasm has been discussed.

Iron deficiency anaemia: Effect on congnitive development in children: A review.

Iron deficiency evolves slowly through several stages. Early iron deficiency caused a depletion in iron stores as shown by a reduction in the levels of hepatic non-heme iron in the new born of iron deficient mothers. Of particular importance is the effect on central nervous system, which leads to the defects in the cognition and learning processes in humans. Evidence is strong that in many under developed countries iron deficiency is the main cause of anaemia and supplementation under trial conditions may prevent some defects of iron deficiency but not all.

Effect of iron deficiency on developing rat brain.

Iron deficiency evolves, slowly through several stages. Early iron deficiency caused a depletion in iron stores as shown by a reduction in the levels of hepatic non heme iron (44%) in the 7 days old pups born to iron deficient mothers. The hemoglobin levels and PCV (packed cell volume) were significantly reduced only after the age of three weeks. The activities of GABA (γ-amino butyric acid) shunt enzymes viz. GDH, GAD and GABA-T (glutamate dehydrogenase, glutamate decarboxylase and GABA-transaminase, respectively) and GABA content were found to decrease during gestation and/or lactation iron deficiency at 1 week (wk), 2wk, 3wk and 4wk of age in the developing rat brains. However GABA binding showed a significant increase at different age groups. The iron deficiency during lactational exposure showed significant alteration in most of the parameters only at the age of 3 weeks onwards. On rehabilitation with iron supplemented diet for 2 weeks, these altered parameters could not attain corresponding control values. A prolonged iron deficiency causing alterations in GABA may lead to neurological and behavioral alterations.